DOCSLIB.ORG

Tobin Roy Sosnick Department of Biochemistry and Molecular Biology

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Tobin Roy Sosnick Department of Biochemistry and Molecular Biology Tobin Roy Sosnick Department of Biochemistry and Molecular Biology The University of Chicago Telephone: (773) 834-0657 929 East 57th Street Fax: (773) 702-0439 Chicago, Illinois 60637 [email protected] Education 1989 Ph.D., Applied Physics, Harvard University, “Momentum Distribution of Normal and Superfluid Helium Using Inelastic Neutron Scattering” 1985 M.S., Applied Physics, Harvard University 1983 B.A., Physics, University of California, San Diego Professional Experience 8/11-present Chair, Dept. of Biochemistry and Molecular Biology 10/13-present Fellow, Institute for Molecular Engineering 2009-12/11 Director, Institute for Biophysical Dynamics, University of Chicago 3/08-present Senior Fellow, Computation Institute, University of Chicago 3/07-present Professor, University of Chicago 3/06-present Chair, Graduate Program in Biophysical Sciences 5/98-present Institute for Biophysical Dynamics, University of Chicago, founding member 9/96-6/03-3/07 Assistant, Associate Professor, University of Chicago 1/96-6/96 Research Assistant Professor, University of Pennsylvania 1992-1995 Postdoctoral fellow with Prof. S.W. Englander, University of Pennsylvania 1991-1992 Postdoctoral fellow with Dr. C. Unkefer, Los Alamos National Lab 1988-1991 Postdoctoral fellow with Dr. J. Trewhella, Los Alamos National Lab 1984-1988 Predoctoral fellow with Prof. P. Sokol, Harvard University Publications 1. Riback, J. A., Bowman, M. A., Zmyslowski, A. M., Knoverek, C. R., Jumper, J. M., Hinshaw, J. R., Kaye, E. B., Freed, K. F., Clark, P. L., and Sosnick, T. R. (2017) Innovative scattering analysis shows that hydrophobic disordered proteins are expanded in water, Science 358, 238- 241. 2. Riback, J. A., Katanski, C. D., Kear-Scott, J. L., Pilipenko, E. V., Rojek, A. E., Sosnick, T. R., and Drummond, D. A. (2017) Stress-Triggered Phase Separation Is an Adaptive, Evolutionarily Tuned Response, Cell 168, 1028-1040 e1019. PMC5401687 3. Gates, Z. P., Baxa, M. C., Yu, W., Riback, J. A., Li, H., Roux, B., Kent, S. B., and Sosnick, T. R. (2017) Perplexing cooperative folding and stability of a low-sequence complexity, polyproline 2 protein lacking a hydrophobic core, Proc Natl Acad Sci U S A. PMC5338553 4. French, A. R., Sosnick, T. R., and Rock, R. S. (2017) Investigations of human myosin VI targeting using optogenetically controlled cargo loading, Proc Natl Acad Sci U S A 114, E1607- E1616. PMC5338507 5. Skinner, J. J., Wang, S., Lee, J., Ong, C., Sommese, R., Sivaramakrishnan, S., Koelmel, W., Hirschbeck, M., Schindelin, H., Kisker, C., Lorenz, K., Sosnick, T. R., and Rosner, M. R. (2017) A conserved salt bridge competition triggered by phosphorylation regulates the protein interactome, Proc. Natl. Acad. Sci. U S A. 6. Sachleben, J. R., Adhikari, A. N., Gawlak, G., Hoey, R. J., Liu, G., Joachimiak, A., Montelione, G. T., Sosnick, T. R., and Koide, S. (2017) Aromatic claw: A new fold with high aromatic content that evades structural prediction, Protein Sci 26, 208-217. PMC5275723 7. Poellmann, M. J., Sosnick, T. R., Meredith, S. C., and Lee, R. C. (2017) The Pentablock Amphiphilic Copolymer T1107 Prevents Aggregation of Denatured and Reduced Lysozyme, Macromol Biosci 17. PMC5497315 Sosnick CV p. 1 8. Yu, W., Baxa, M. C., Gagnon, I., Freed, K. F., and Sosnick, T. R. (2016) Cooperative folding near the downhill limit determined with amino acid resolution by hydrogen exchange, Proc Natl Acad Sci U S A. PMCID 4855600 9. Virtanen, J. J., Sosnick, T. R., and Freed, K. F. (2016) Erratum: "Ionic strength independence of charge distributions in solvation of biomolecules" [J. Chem. Phys. 141, 22D503 (2014)], J Chem Phys 145, 059903. PMC4975747 10. Basanta, B., Chan, K. K., Barth, P., King, T., Hinshaw, J. R., Sosnick, T. R., Liu, G., Everett, J., Xiao, R., Montelione, G. T., and Baker, D. (2016) Introduction of a polar core into the de novo designed protein Top7, Protein Sci. PMCID 4918430 11. Watkins, H. M., Simon, A. J., Sosnick, T. R., Lipman, E. A., Hjelm, R. P., and Plaxco, K. W. (2015) Random coil negative control reproduces the discrepancy between scattering and FRET measurements of denatured protein dimensions, Proc Natl Acad Sci U S A 112, 6631-6636. PMCID 4450392 12. Baxa, M. C., Yu, W., Adhikari, A. N., Ge, L., Xia, Z., Zhou, R., Freed, K. F., and Sosnick, T. R. (2015) Even with nonnative interactions, the updated folding transition states of the homologs Proteins G & L are extensive and similar, Proc Natl Acad Sci U S A 112, 8302-8307. PMCID 4500205 13. Zayner, J. P., and Sosnick, T. R. (2014) Factors that control the chemistry of the LOV domain photocycle, PLoS One 9, e87074. PMCID 3903614 14. Virtanen, J. J., Sosnick, T. R., and Freed, K. F. (2014) Ionic strength independence of charge distributions in solvation of biomolecules, J Chem Phys 141, 22D503. PMCID 4169388 15. Skinner, J. J., Yu, W., Gichana, E. K., Baxa, M. C., Hinshaw, J. R., Freed, K. F., and Sosnick, T. R. (2014) Benchmarking all-atom simulations using hydrogen exchange, Proc Natl Acad Sci U S A 111, 15975-15980. PMCID 4234613 16. Baxa, M. C., Haddadian, E. J., Jumper, J. M., Freed, K. F., and Sosnick, T. R. (2014) Loss of conformational entropy in protein folding calculated using realistic ensembles and its implications for NMR-based calculations, Proc Natl Acad Sci U S A 111, 15396-15401. PMCID 4217416 17. Zayner, J. P., Antoniou, C., French, A. R., Hause, R. J., Jr., and Sosnick, T. R. (2013) Investigating models of protein function and allostery with a widespread mutational analysis of a light-activated protein, Biophys J 105, 1027-1036. PMCID 3752136 18. Walters, B. T., Mayne, L., Hinshaw, J. R., Sosnick, T. R., and Englander, S. W. (2013) Folding of a large protein at high structural resolution, Proc Natl Acad Sci U S A 110, 18898-18903. PMCID 3839771 19. Sosnick, T. R., and Baxa, M. C. (2013) Revealing what gets buried first in protein folding, Proc Natl Acad Sci U S A 110, 16704-16705. PMCID 3801029 20. Sanchez-Rodriguez, J. E., Khalili-Araghi, F., Adhikari, A., Sosnick, T., Roux, B., Holmgren, M., and Bezanilla, F. (2013) Probing Conformational Changes of the Na+/K+ ATPase upon Ouabain Binding by using a Spectroscopic Approach, Biophys. J. 104, 300A-300A. 21. Parisien, M., Wang, X., Perdrizet, G., 2nd, Lamphear, C., Fierke, C. A., Maheshwari, K. C., Wilde, M. J., Sosnick, T. R., and Pan, T. (2013) Discovering RNA-protein interactome by using chemical context profiling of the RNA-protein interface, Cell Rep 3, 1703-1713. PMCID 3769137 22. Liu, Y., Haddadian, E., Sosnick, T. R., Freed, K. F., and Gong, H. (2013) A Novel Implicit Solvent Model for Simulating the Molecular Dynamics of RNA, Biophys. J. 105, 1248-1257. PMCID 3762369 23. Adhikari, A. N., Freed, K. F., and Sosnick, T. R. (2013) Simplified protein models: predicting folding pathways and structure using amino acid sequences, Phys Rev Lett 111, 028103. PMCID 4047675 24. Zayner, J. P., Antoniou, C., and Sosnick, T. R. (2012) The Amino-Terminal Helix Modulates Light-Activated Conformational Changes in AsLOV2, J. Mol. Biol. 419, 61-74. PMCID: PMC3338903 Sosnick CV p. 2 25. Yoo, T. Y., Meisburger, S. P., Hinshaw, J., Pollack, L., Haran, G., Sosnick, T. R., and Plaxco, K. (2012) Small-angle X-ray scattering and single-molecule FRET spectroscopy produce highly divergent views of the low-denaturant unfolded state, J. Mol. Biol. 418, 226-236. PMCID 3523729 26. Yoo, T. Y., Adhikari, A., Xia, Z., Huynh, T., Freed, K. F., Zhou, R., and Sosnick, T. R. (2012) The folding transition state of protein L is extensive with nonnative interactions (and not small and polarized), J. Mol. Biol. 420, 220-234. PMCID 3372659 27. Strickland, D., Lin, Y., Wagner, E., Hope, C. M., Zayner, J., Antoniou, C., Sosnick, T. R., Weiss, E. L., and Glotzer, M. (2012) TULIPs: tunable, light-controlled interacting protein tags for cell biology, Nature Meth. 9, 379-384. PMCID: PMC3444151 28. Shandiz, A. T., Baxa, M. C., and Sosnick, T. R. (2012) A "Link-Psi" strategy using crosslinking indicates that the folding transition state of ubiquitin is not very malleable, Prot. Sci. 21, 819-827. PMCID: PMC3403417 29. Perdrizet, G. A., 2nd, Artsimovitch, I., Furman, R., Sosnick, T. R., and Pan, T. (2012) Transcriptional pausing coordinates folding of the aptamer domain and the expression platform of a riboswitch, Proc. Natl. Acad. Sci. U S A 109, 3323-3328. PMCID: PMC3295289 30. Parisien, M., Freed, K. F., and Sosnick, T. R. (2012) On docking, scoring and assessing protein- DNA complexes in a rigid-body framework, PLoS One 7, e32647. PMCID: PMC3290582 31. DeBartolo, J., Jha, A., Freed, K. F., and Sosnick, T. R. (2012) Local Backbone Preferences and Nearest-Neighbor Effects in the Unfolded and Native States, In Protein and Peptide Folding, Misfolding, and Non-Folding, pp 79-98, John Wiley & Sons, Inc. 32. Baxa, M. C., Haddadian, E. J., Jha, A. K., Freed, K. F., and Sosnick, T. R. (2012) Context and Force Field Dependence of the Loss of Protein Back-bone Entropy upon Folding Using Realistic Denatured and Native State Ensembles., J. Am. Chem. Soc. 134, 15929-15936. PMCID: PMC3464005 33. Adhikari, A. N., Peng, J., Wilde, M., Xu, J., Freed, K. F., and Sosnick, T. R. (2012) Modeling large regions in proteins: Applications to loops, termini, and folding, Protein Sci. 21, 107-121. PMCID 3323786 34. Adhikari, A., Freed, K. F., and Sosnick, T. R. (2012) De novo prediction of protein folding pathways and structure using the principle of sequential stabilization, Proc. Natl. Acad. Sci. U S A 109, 17442-17447. PMCID 3491489 35. Virtanen, J. J., Makowski, L., Sosnick, T. R., and Freed, K. F. (2011) Modeling the Hydration Layer around Proteins: Applications to Small- and Wide-Angle X-Ray Scattering, Biophys.
Load more

Recommended publications
  • Single-Molecule Spectroscopy and Imaging Studies of Protein Folding-Unfolding Conformational Dynamics: the Multiple-State and Multiple-Channel Energy Landscape
    SINGLE-MOLECULE SPECTROSCOPY AND IMAGING STUDIES OF PROTEIN FOLDING-UNFOLDING CONFORMATIONAL DYNAMICS: THE MULTIPLE-STATE AND MULTIPLE-CHANNEL ENERGY LANDSCAPE Zijian Wang A Dissertation Submitted to the Graduate College of Bowling Green State University in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY May 2016 Committee: H. Peter Lu, Advisor Gabriela Bidart-Bouzat Graduate Faculty Representative Ksenija D. Glusac George Bullerjahn © 2016 Zijian Wang All Rights Reserved iii ABSTRACT H. Peter Lu, Advisor Protein conformational dynamics often plays a critical role in protein functions. We have characterized the spontaneous folding-unfolding conformational fluctuation dynamics of calmodulin (CaM) at thermodynamic equilibrium conditions by using single-molecule fluorescence resonance energy transfer (FRET) spectroscopy. We studied protein folding dynamics under simulated biological conditions to gain a deep, mechanistic understanding of this important biological process. We have identified multiple folding transition pathways and characterized the underlying energy landscape of the single-molecule protein conformational fluctuation trajectories. Our results suggest that the folding dynamics of CaM molecules involves a complex multiple-pathway multiple-state energy landscape, rather than an energy landscape of two-state dynamical process. Our probing single-molecule FRET fluctuation experiments demonstrate a new approach of studying spontaneous protein folding-unfolding conformational dynamics at the equilibrium that features recording long time single-molecule conformational fluctuation trajectories. This technique yields rich statistical and dynamical information far beyond traditional ensemble-averaged measurements. We characterize the conformational dynamics of single CaM interacting with C28W. The single CaM molecules are partially unfolded by GdmCl, and the folded and unfolded CaM molecules are approximately equally populated.
    [Show full text]
  • Exploring the Effects of Hydrogen Bonding and Hydrophobic
    Chemical Physics 307 (2004) 187–199 www.elsevier.com/locate/chemphys Exploring the effects of hydrogen bonding and hydrophobic interactions on the foldability and cooperativity of helical proteins using a simplified atomic model Michael Knott, Hue Sun Chan * Protein Engineering Network of Centres of Excellence (PENCE), Department of Biochemistry, 1 Kings College Circle, University of Toronto, Toronto, Ont., Canada M5S 1A8 Department of Medical Genetics and Microbiology, Faculty of Medicine, University of Toronto, Toronto, Ont., Canada M5S 1A8 Received 16 February 2004; accepted 3 June 2004 Available online 6 July 2004 Abstract Using a simplified atomic model, we perform Langevin dynamics simulations of polypeptide chains designed to fold to one-, two- and three-helix native conformations. The impact of the relative strengths of the hydrophobic and hydrogen bonding interactions on folding is investigated. Provided that the two interactions are appropriately balanced, a simple potential function allows the chains to fold to their respective target native structures, which are essentially lowest-energy conformations. However, if the hydrophobic interaction is too strong, helix formation is preempted by hydrophobic collapse into compact conformations with little helical content. While the transition from denatured to compact non-native conformations is not cooperative, the transition between native (helical) and denatured states exhibits certain cooperative features. The degree of apparent cooperativity increases with the length of the polypeptide; but it falls far short of that observed experimentally for small, single-domain ‘‘two-state’’ proteins. Even for the three-helix bundle, the present model interaction scheme leads to a distribution of energy which is not bimodal, although a heat capacity peak associated with thermal unfolding is observed.
    [Show full text]
  • Protein Folding: New Methods Unveil Rate-Limiting Structures
    UNIVERSITY OF CHICAGO PROTEIN FOLDING: NEW METHODS UNVEIL RATE-LIMITING STRUCTURES A DISSERTATION SUBMITTED TO THE FACULTY OF THE DIVISION OF THE BIOLOGICAL SCIENCES AND THE PRITZKER SCHOOL OF MEDICINE IN CANDIDACY FOR THE DEGREE OF DOCTOR OF PHILOSOPHY DEPARTMENT OF BIOCHEMISTRY AND MOLECULAR BIOLOGY BY BRYAN ANDREW KRANTZ CHICAGO, ILLINOIS AUGUST 2002 Copyright © 2002 by Bryan Andrew Krantz All rights reserved ii TO MY WIFE, KRIS, AND MY FAMILY iii Table of Contents Page List of Figures viii List of Tables x List of Abbreviations xi Acknowledgements xii Abstract xiii Chapter 1.0 Introduction to Protein Folding 1 1.1 Beginnings: Anfinsen and Levinthal 1 1.1.1 Intermediates populated by proline isomerization 2 1.1.2 Intermediates populated by disulfide bond formation 4 1.1.3 H/D labeling folding intermediates 7 1.1.4 Kinetically two-state folding 8 1.2 Present thesis within historical context 11 1.3 The time scales 12 1.3.1 From microseconds to decades 12 1.3.2 A diffusive process 13 1.3.3 Misfolding and chaperones 13 1.4 The energies 14 1.4.1 The hydrophobic effect 14 1.4.2 Conformational entropy 15 1.4.3 Hydrogen bonds 15 1.4.4 Electrostatics 16 1.4.5 Van der Waals 19 1.5 Surface burial 19 1.6 Modeling protein folding 20 1.6.1 Diffusion-collision and hydrophobic collapse 21 1.6.2 Search nucleation 22 1.6.3 Are there intermediates? 23 1.6.4 Pathways or landscapes? 27 2.0 The Initial Barrier Hypothesis in Protein Folding 30 2.1 Abstract 30 2.2 Introduction 30 2.3 Early intermediates 41 2.3.1 Cytochrome c 41 2.3.2 Barnase 46 2.3.3 Ubiquitin
    [Show full text]
  • Cooperative Folding Kinetics of BBL Protein and Peripheral Subunit-Binding Domain Homologues
    Cooperative folding kinetics of BBL protein and peripheral subunit-binding domain homologues Wookyung Yu*, Kwanghoon Chung*†, Mookyung Cheon*‡, Muyoung Heo*§, Kyou-Hoon Han¶, Sihyun Hamʈ, and Iksoo Chang*,** *National Research Laboratory for Computational Proteomics and Biophysics, Department of Physics, Pusan National University, Busan 609-735, Korea; ‡Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom; ¶Molecular Cancer Research Center, Korea Research Institute for Bioscience and Biotechnology, Daejeon 305-806, Korea; and ʈDepartment of Chemistry, Sookmyoung Women’s University, Seoul 140-742, Korea Edited by Alan R. Fersht, University of Cambridge, Cambridge, United Kingdom, and approved December 21, 2007 (received for review September 7, 2007) Recent experiments claiming that Naf-BBL protein follows a global energy landscape when the folding energy predominates over the downhill folding raised an important controversy as to the folding loss of the conformational entropy (4), depending upon the mechanism of fast-folding proteins. Under the global downhill conditions of a folding experiment such as their initial locations folding scenario, not only do proteins undergo a gradual folding, on the free energy landscape and the heterogeneity of confor- but folding events along the continuous folding pathway also mational ensemble (7). In the global downhill folding model the could be mapped out from the equilibrium denaturation experi- folding free energy landscape possesses a global unimodal ment. Based on the exact calculation using a free energy landscape, distribution for all denaturation conditions so that a protein relaxation eigenmodes from a master equation, and Monte Carlo follows a smooth and progressive conformational change, and a simulation of an extended Muñoz–Eaton model that incorporates continuous folding pathway can be observed simply by an multiscale-heterogeneous pairwise interactions between amino equilibrium denaturation experiment (11, 12).
    [Show full text]
  • “Strange Kinetics” of Ubiquitin Folding: Interpretation in Terms of a Simple Kinetic Model
    Computational structural and functional proteomics 243 Chapter # “STRANGE KINETICS” OF UBIQUITIN FOLDING: INTERPRETATION IN TERMS OF A SIMPLE KINETIC MODEL Chekmarev S.F.*1, Krivov S.V.2, Karplus M.2, 3* 1 Institute of Thermophysics, SB RAS, Novosibirsk, 630090, Russia; 2 Laboratoire de Chimie Biophysique, ISIS, Université Louis Pasteur, 67000, Strasbourg, France; 3 Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA, e-mail: [email protected] * Corresponding authors: e-mail: [email protected] Key words: ubiquitin, folding, folding times, rate constants, kinetic model, experiment SUMMARY Motivation: Interpretation of protein folding experiments in terms of the transitions between characteristic states of the system may allow valuable insight into the folding mechanism. Results: The ubiquitin mutant Ub*G folding experiments of Sabelko et al. (1999), in which “strange kinetics” were observed, are interpreted in terms of a simple kinetic model. A minimal set of states consisting of a semi-compact globule, two off-pathway traps, and the native state are included. Both the low and high temperature experiments of Sabelko et al. are fitted by a system of kinetic equations determining the transitions between these states. It is possible that cold and heat denaturated states of Ub*G are the basis of the off-pathway traps. The fits of the kinetic model to the experimental results provides an estimate of the rate constants for the various reaction channels and show how their contributions vary with temperature. Introduction of an on-pathway intermediate instead of one of the off-pathway traps does not lead to agreement with the experiments.
    [Show full text]
  • Statistical Mechanics of a Correlated Energy Landscape Model for Protein Folding Funnels Steven S
    Statistical mechanics of a correlated energy landscape model for protein folding funnels Steven S. Plotkin, Jin Wang, and Peter G. Wolynes Department of Physics and School of Chemical Sciences, University of Illinois, Urbana, Illinois 61801 ~Received 31 May 1996; accepted 6 November 1996! In heteropolymers, energetic correlations exist due to polymeric constraints and the locality of interactions. Pair correlations in conjunction with the a priori specification of the existence of a particularly low energy state provide a method of introducing the aspect of minimal frustration to the energy landscapes of random heteropolymers. The resulting funneled landscape exhibits both a phase transition from a molten globule to a folded state, and the heteropolymeric glass transition in the globular state. We model the folding transition in the self-averaging regime, which together with a simple theory of collapse allows us to depict folding as a double-well free energy surface in terms of suitable reaction coordinates. Observed trends in barrier positions and heights with protein sequence length and thermodynamic conditions are discussed within the context of the model. We also discuss the new physics which arises from the introduction of explicitly cooperative many-body interactions, as might arise from sidechain packing and nonadditive hydrophobic forces. © 1997 American Institute of Physics. @S0021-9606~97!52406-8# I. INTRODUCTION teins have used much of the mathematical techniques used to treat spin glasses6 and regular magnetic systems.7 The poly- Molecular scientists view protein folding as a complex meric nature of the problem must also be taken into account. chemical reaction. Another fruitful analogy from statistical Mean field theories based on replica techniques8 and varia- physics is that folding resembles a phase transition in a finite tional methods9 have been very useful, but are more difficult system.
    [Show full text]
  • Cooperative Folding Kinetics of BBL Protein and Peripheral Subunit-Binding Domain Homologues
    Cooperative folding kinetics of BBL protein and peripheral subunit-binding domain homologues Wookyung Yu*, Kwanghoon Chung*†, Mookyung Cheon*‡, Muyoung Heo*§, Kyou-Hoon Han¶, Sihyun Hamʈ, and Iksoo Chang*,** *National Research Laboratory for Computational Proteomics and Biophysics, Department of Physics, Pusan National University, Busan 609-735, Korea; ‡Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom; ¶Molecular Cancer Research Center, Korea Research Institute for Bioscience and Biotechnology, Daejeon 305-806, Korea; and ʈDepartment of Chemistry, Sookmyoung Women’s University, Seoul 140-742, Korea Edited by Alan R. Fersht, University of Cambridge, Cambridge, United Kingdom, and approved December 21, 2007 (received for review September 7, 2007) Recent experiments claiming that Naf-BBL protein follows a global energy landscape when the folding energy predominates over the downhill folding raised an important controversy as to the folding loss of the conformational entropy (4), depending upon the mechanism of fast-folding proteins. Under the global downhill conditions of a folding experiment such as their initial locations folding scenario, not only do proteins undergo a gradual folding, on the free energy landscape and the heterogeneity of confor- but folding events along the continuous folding pathway also mational ensemble (7). In the global downhill folding model the could be mapped out from the equilibrium denaturation experi- folding free energy landscape possesses a global unimodal ment. Based on the exact calculation using a free energy landscape, distribution for all denaturation conditions so that a protein relaxation eigenmodes from a master equation, and Monte Carlo follows a smooth and progressive conformational change, and a simulation of an extended Muñoz–Eaton model that incorporates continuous folding pathway can be observed simply by an multiscale-heterogeneous pairwise interactions between amino equilibrium denaturation experiment (11, 12).
    [Show full text]
  • A Natural Missing Link Between Activated and Downhill Protein Folding Scenarios
    A natural missing link between activated and downhill protein folding scenarios Feng Liu, Caroline Maynard, Gregory Scott, Artem Melnykov, Kathleen B. Hall and Martin Gruebele We propose protein PTBl :4W as a good candidate for engineering into a downhill folder. PTBl: 4W has a probe-dependent thermal unfolding curve and sub-millisecond T-jump relaxation kinetics on more than one time scale. Its refolding rate in denaturant is a non-linear function of denaturant concentration (curved chevron plot). Yet at high denaturant concentration its unfolding is probe-independent, and the folding kinetics can be fitted to a single exponential decay. The domain appears to fold via a mechanism between downhill folding and activated folding over several small barriers, and when denaturant is added, one of these barriers greatly increases and simplifies the observed folding to apparent two-state kinetics. We predict the simplest free energy function consistent with the thermai denaturation and kinetics experiments by using the singular value Smoluchowski dynamics (SVSD) model. PTBl: 4W is a natural 'missing link' between downhill and activated folding. We suggest mutations that could move the protein into the downhill folding limit. 18 19 Introduction downhill folders, • and even downhill folders at the melting transition.20 The experimental detection of the protein folding 'speed limit' A good starting point for such engineering is a wild type 1 3 and of downhill folding - has attracted great interest among protein with a broad probe-dependent melting transition (low 4 5 6 7 simulators, • theorists, • and the community interested in cooperativity), yet fast folding rate (sub-millisecond).
    [Show full text]
  • The Change of Conditions Does Not Affect Ros87 Downhill Folding
    www.nature.com/scientificreports OPEN The change of conditions does not afect Ros87 downhill folding mechanism Rinaldo Grazioso1, Sara García‑Viñuales2, Gianluca D’Abrosca1, Ilaria Baglivo1, Paolo Vincenzo Pedone1, Danilo Milardi2, Roberto Fattorusso1, Carla Isernia1, Luigi Russo1* & Gaetano Malgieri1* Downhill folding has been defned as a unique thermodynamic process involving a conformations ensemble that progressively loses structure with the decrease of protein stability. Downhill folders are estimated to be rather rare in nature as they miss an energetically substantial folding barrier that can protect against aggregation and proteolysis. We have previously demonstrated that the prokaryotic zinc fnger protein Ros87 shows a bipartite folding/unfolding process in which a metal binding intermediate converts to the native structure through a delicate barrier‑less downhill transition. Signifcant variation in folding scenarios can be detected within protein families with high sequence identity and very similar folds and for the same sequence by varying conditions. For this reason, we here show, by means of DSC, CD and NMR, that also in diferent pH and ionic strength conditions Ros87 retains its partly downhill folding scenario demonstrating that, at least in metallo‑proteins, the downhill mechanism can be found under a much wider range of conditions and coupled to other diferent transitions. We also show that mutations of Ros87 zinc coordination sphere produces a diferent folding scenario demonstrating that the organization of the metal ion core is determinant in the folding process of this family of proteins. Protein folding is essentially an exploration of conformational space on a funneled energy surface. Several small protein domains fold by two-state equilibrium mechanisms 1.
    [Show full text]
  • Reversible Two-State Folding of the Ultrafast Protein Gpw Under Mechanical Force
    bioRxiv preprint doi: https://doi.org/10.1101/314583; this version posted May 5, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Reversible two-state folding of the ultrafast protein gpW under mechanical force Authors: Jörg Schönfelder1‡, David De Sancho,2‡, Ronen Berkovich3, Robert B. Best4, Victor Muñoz5,6,7,* and Raul Perez-Jimenez1,8,* Affiliations: 1CIC nanoGUNE, 20018 San Sebastián, Spain 2Kimika Fakultatea, Euskal Herriko Unibertsitatea (UPV/EHU) and Donostia International Physics Center (DIPC), P.K. 1072, 20080 Donostia, Spain 3Department of Chemical Engineering, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel 4Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0520, United States 5National Biotechnology Center, Consejo Superior de Investigaciones Científicas, Darwin 3, Campus de Cantoblanco, 28049 Madrid, Spain 6IMDEA Nanosciences, Faraday 9, Ciudad Universitaria Cantoblanco, 28049 Madrid, Spain 7Department of Bioengineering, University of California, 95343 Merced, California, USA 8IKERBASQUE, Basque Foundation for Science, 48013 Bilbao, Spain *Correspondence to: V.M ([email protected]) and R.P-J. ([email protected]) 1 bioRxiv preprint doi: https://doi.org/10.1101/314583; this version posted May 5, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license.
    [Show full text]
  • New Methods to Assess Protein Folding and Conformational Dynamics
    University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations 2016 New Methods To Assess Protein Folding And Conformational Dynamics Chun-Wei Lin University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Biophysics Commons, and the Physical Chemistry Commons Recommended Citation Lin, Chun-Wei, "New Methods To Assess Protein Folding And Conformational Dynamics" (2016). Publicly Accessible Penn Dissertations. 2425. https://repository.upenn.edu/edissertations/2425 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/2425 For more information, please contact [email protected]. New Methods To Assess Protein Folding And Conformational Dynamics Abstract A protein’s folding and conformational energy landscape depends on a large number of molecular degrees of freedom and interactions. As a result, different proteins can follow different sequences of events moving toward the native state along the course of folding. For example, the underlying structural organization and ordering can occur locally first and then globally, or vice versa. In addition, the associated conformational transitions can take place over a wide range of timescales. Because of these complexities, arriving at a detailed assessment and understanding of the folding dynamics and mechanism of any protein via a single type of experiment is challenging, and sometimes impossible. As such, over the past two decades, many different experimental methods have been employed to study how proteins fold among which, the laser-induced temperature-jump (T-jump) technique has emerged as a powerful tool to measure protein folding kinetics occurring on the nanosecond and microsecond timescales. Herein, we further expand the utility of the T-jump technique.
    [Show full text]
  • The Protein Folding Problem
    The Protein Folding Problem Ken A. Dill,1,2 S. Banu Ozkan,3 M. Scott Shell,4 and Thomas R. Weikl5 1Department of Pharmaceutical Chemistry, 2Graduate Group in Biophysics, University of California, San Francisco, California 94143; email: [email protected] 3Department of Physics, Arizona State University, Tempe, Arizona 85287; email: [email protected] 4Department of Chemical Engineering, University of California, Santa Barbara, California 93106; email: [email protected] 5Max Planck Institute of Colloids and Interfaces, Department of Theory and Bio-Systems, 14424 Potsdam, Germany; email: [email protected] Annu. Rev. Biophys. 2008. 37:289–316 Key Words The Annual Review of Biophysics is online at structure prediction, funnel energy landscapes, CASP, folding biophys.annualreviews.org code, folding kinetics This article’s doi: 10.1146/annurev.biophys.37.092707.153558 Abstract Copyright c 2008 by Annual Reviews. The “protein folding problem” consists of three closely related puz- All rights reserved zles: (a) What is the folding code? (b) What is the folding mechanism? 1936-122X/08/0609-0289$20.00 (c) Can we predict the native structure of a protein from its amino acid sequence? Once regarded as a grand challenge, protein fold- ing has seen great progress in recent years. Now, foldable proteins and nonbiological polymers are being designed routinely and mov- ing toward successful applications. The structures of small proteins are now often well predicted by computer methods. And, there is now a testable explanation for how a protein can fold so quickly: A protein solves its large global optimization problem as a series of smaller local optimization problems, growing and assembling the native structure from peptide fragments, local structures first.
    [Show full text]